Investigation on the binding behavior between BSA and lenvatinib with the help of various spectroscopic and in silico methods

Lenvatinib was a multi-tyrosine kinase inhibitor (TKI) used for treating advanced renal cell carcinoma and differentiated thyroid cancer. Multiple fluorescence spectroscopy including SSF, SF, 3DF, UV, FTIR, and molecular modeling were utilized for better understanding the binding interaction between lenvatinib and bovine serum albumin (BSA). SSF spectroscopy results showed lenvatinib quenched the intrinsic fluorescence of BSA in the form of the mixed mechanism. The binding constants (Kb) of lenvatinib on BSA were about 104 M−1, indicating the affinity on BSA was moderate. Based on the analysis of the thermodynamic parameters, it can be inferred that lenvatinib spontaneously binds onto BSA and the hydrogen bonding and hydrophobic interactions are responsible for both bindings. The outcomes of UV, SF spectroscopy and FTIR showed the conformational change of BSA was caused due to binding lenvatinib. The outcomes of the molecular docking revealed that lenvatinib inserted into the hydrophobic groove between sub-domain IIA, IIB and IIIA, which further demonstrated the competition experiments result of ibuprofen and phenylbutazone markers. Furthermore, molecular docking and molecular dynamics (MD) simulations were performed to investigate the binding behavior of lenvatinib with BSA. The effect of some ions such as K+, Cu 2+, Ca2+, Mg2+, Ni2+, Zn2+ and Fe3+ on the binding affinity was also discussed. [Display omitted] •Lenvatinib binding onto BSA was explored through spectroscopic, docking and MD simulation.•Affinity of lenvatinib on BSA was moderate with the Kb of about 104 M−1 order.•Lenvatinib bound to the hydrophobic groove between sub-domain IIA, IIB and IIIA.•Alteration in the conformation of BSA occurred after interaction between two.•The contribution of residues to forming the stable lenvatinib-BSA complex was analyzed.